Binding of ATP to Human DNA topoisomerase i resulting in an alteration of conformation and catalytic activity of the enzyme

Jhutlang Hwang, Huî Jye Chen

Research output: Contribution to journalArticle

Abstract

Wo have studied the molecular mechanism of A IP-inhibitory effect on the DNA relaxation activity of human DNA topoisomerase I. We have demon si rated that ATP directly and specifically binds to human DNA topoisonierasc I. To address the question whether the DNA relaxation activity of human UNA topoisomerase 1 was allosterically regulated by ATP, We examined the confor [national change of human DNA topoisomerase 1 upon ATP binding. Human !)NA topoisomerase I was incubated with various concentrations of ATP prior ID the treatment by various proteinases, such as trypsin. chymotrypsin. t her molysin. \'K protease, and proleinase K. Our results show that in the presence of ATP. human DNA topoisomerase I becomes resistant towards degradation by trypsin and chymotrypsin, suggesting that the conformation of human DXA lopoisoincrase I becomes alterated upon ATP binding. This observation suggests that DNA topoisomerase I exhibits at least two conformations. Onr con formation is in the form of Topo I-ATP complex, which executes protein kinasc activity, and t lie other is in thr form of Topo [-DNA complex, which executes DNA relaxation activity.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number8
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

DNA topoisomerase
Type I DNA Topoisomerase
catalytic activity
Conformations
Catalyst activity
Adenosine Triphosphate
Enzymes
enzymes
DNA
chymotrypsin
trypsin
proteinases
Endopeptidase K
Chymotrypsin
Human Activities
Trypsin
Peptide Hydrolases
Degradation
degradation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Binding of ATP to Human DNA topoisomerase i resulting in an alteration of conformation and catalytic activity of the enzyme. / Hwang, Jhutlang; Chen, Huî Jye.

In: FASEB Journal, Vol. 12, No. 8, 1998.

Research output: Contribution to journalArticle

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